Bosse Folkert, Marcaurelle Lisa A, Seeberger Peter H
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
J Org Chem. 2002 Sep 20;67(19):6659-70. doi: 10.1021/jo025834+.
The tumor-associated carbohydrate antigens Globo-H, SSEA-3, and Gb3 were synthesized in a linear fashion using glycosyl phosphate monosaccharide building blocks. All of the building blocks were prepared from readily available common precursors. The difficult alpha-(1-->4-cis)-galactosidic linkage was installed using a galactosyl phosphate donor with high selectivity. Introduction of the beta-galactosamine unit required the screening a variety of amine protecting groups to ensure good donor reactivity and protecting group compatibility. An N-trichloroacetyl-protected galactosamine donor performed best for the installation of the beta-glycosidic linkage. Conversion of the trichloroacetyl group to the N-acetyl group was achieved under mild conditions, fully compatible with the presence of multiple glycosidic bonds. This synthetic strategy is expected to be amenable to the synthesis of the globo-series of tumor antigens on solid-support.
肿瘤相关碳水化合物抗原Globo-H、阶段特异性胚胎抗原-3（SSEA-3）和3-O-磺基神经节苷脂（Gb3）采用磷酸单糖构建模块以线性方式合成。所有构建模块均由易于获得的常见前体制备而成。利用具有高选择性的磷酸半乳糖供体形成困难的α-(1→4-顺式)-半乳糖苷键。引入β-半乳糖胺单元需要筛选多种胺保护基团，以确保良好的供体反应性和保护基团兼容性。N-三氯乙酰基保护的半乳糖胺供体在形成β-糖苷键方面表现最佳。三氯乙酰基向N-乙酰基的转化在温和条件下实现，与多个糖苷键的存在完全兼容。预计这种合成策略适用于在固相载体上合成globoseries肿瘤抗原。
